Virtual pathology: Reaching higher standards for noninvasive CTA tissue characterization capability by using histology as a truth standard.

AIMS: Despite advances in therapy, reduction in myocardial infarction or death remains elusive. Whereas computed tomography angiography (CTA) is increasingly appreciated, the analyses are often subjective or qualitative. Methods for specific tissue characterization using histopathologic correlates have recently been reported. We extend this here to demonstrate accurate discrimination between, and quantitation of, lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), and fibrotic tissues. METHODS: NCT02143102 collected 576 tissue samples with paired CTA. Cardiovascular pathologists annotated LRNC, IPH, and dense calcification (CALC) regions as a reference standard. Blinded to histology, CTA was analyzed using ElucidVivo (Elucid Bioimaging Inc., Boston, MA USA). Structure and tissue characteristics of atherosclerotic plaque from CTA, accounting for both the imaging acquisition process and the biology, accounting for differences in density distributions that result from the different cellular and molecular level milieu of the relevant tissue types. RESULTS: LRNC was tested across a true range of 0-10 mm2, with a difference of 0.15 mm2 and a slope of 0.92. IPH was tested across a true range of 0-18 mm2, with a difference from histology of 1.68 mm2 and a slope of 0.95. CALC was tested across a range of 0-14 mm2, with a difference of -0.06 mm2 and a slope of 0.99. Matrix tissue (MATX) was tested across a range of 4-52 mm2, with a difference of 0.02 mm2 and a slope of 0.91. CONCLUSION: LRNC, IPH, CALC, and MATX may be objectively quantified using histopathologic correlates automatically from CTA for use singly or in combination to optimize patient care. The availability of objectively validated quantitative markers that may be followed longitudinally may extend the clinical utility of CTA. Additionally, these measures contribute efficacy variables for developing novel drugs and clinical decision support tools for tailored therapeutics.

Lamotrigine and Stevens-Johnson Syndrome Prevention.

Stevens-Johnson Syndrome (SJS) is a rare life-threatening condition characterized by severe mucocutaneous epidermal necrolysis and detachment of the epidermis. The condition centers around a delayed-type hypersensitivity reaction with a complex etiology stemming from a variety of causes. The number one cause is medication-related-common ones including sulfonamides, antiepileptics, allopurinol, and nonsteroidal anti-inflammatory drugs. Genetics also play a role as several human leukocyte antigen (HLA) genotypes within certain ethnic groups have been implicated in adverse reactions to specific drugs. HLAB*15:02 has been identified in the Chinese and others of Southeast Asian origin to increase susceptibility to lamotrigine and carbamazepine-induced SJS. Furthermore, patients of Japanese origin with HLAB*31:01 and Koreans with HLA-B*44:03 are also at increased risk of SJS after receiving the same two drugs. Of the antiepileptics, one most commonly associated with SJS is lamotrigine, a pre-synaptic voltage-gated sodium channel inhibitor. Lamotrigine is an antiepileptic drug of the phenyltriazine class that is indicated for the prevention of focal and generalized seizures in epileptic patients as well as monotherapy or adjunctive maintenance treatment for Bipolar disorder. The occurrence of SJS is not a rigid contraindication to lamotrigine reintroduction in the same patient. To facilitate this, manufacturers have developed a strict re-challenge dosing regimen to facilitate successful reintroduction of lamotrigine. In order to prevent the recurrence of SJS during a re-challenge, timing of re-dose and initial rash severity must be considered. Therefore, to prevent SJS recurrence, prime lamotrigine re-challenge patients are those with mild initial rash that has not occurred within the previous 4 weeks. The Federal Food and Drug Administration recommends the testing HLA subtypes for those associated with SJS prior to starting lamotrigine.